Ligand Binding to Dynamically Populated G-Quadruplex DNA

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00541571" target="_blank" >RIV/68081707:_____/21:00541571 - isvavai.cz</a>

Výsledek na webu

<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202000792" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202000792</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/cbic.202000792" target="_blank" >10.1002/cbic.202000792</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ligand Binding to Dynamically Populated G-Quadruplex DNA

Popis výsledku v původním jazyce

Several small-molecule ligands specifically bind and stabilize G-quadruplex (G4) nucleic acid structures, which are considered to be promising therapeutic targets. G4s are polymorphic structures of varying stability, and their formation is dynamic. Here, we investigate the mechanisms of ligand binding to dynamically populated human telomere G4 DNA by using the bisquinolinium based ligand Phen-DC3 and a combination of single-molecule FRET microscopy, ensemble FRET and CD spectroscopies. Different cations are used to tune G4 polymorphism and folding dynamics. We find that ligand binding occurs to pre-folded G4 structures and that Phen-DC3 also induces G4 formation in unfolded single strands. Following ligand binding to dynamically populated G4s, the DNA undergoes pronounced conformational redistributions that do not involve direct ligand-induced G4 conformational interconversion. On the contrary, the redistribution is driven by ligand-induced G4 folding and trapping of dynamically populated short-lived conformation states. Thus, ligand-induced stabilization does not necessarily require the initial presence of stably folded G4s.

Název v anglickém jazyce

Ligand Binding to Dynamically Populated G-Quadruplex DNA

Popis výsledku anglicky

Several small-molecule ligands specifically bind and stabilize G-quadruplex (G4) nucleic acid structures, which are considered to be promising therapeutic targets. G4s are polymorphic structures of varying stability, and their formation is dynamic. Here, we investigate the mechanisms of ligand binding to dynamically populated human telomere G4 DNA by using the bisquinolinium based ligand Phen-DC3 and a combination of single-molecule FRET microscopy, ensemble FRET and CD spectroscopies. Different cations are used to tune G4 polymorphism and folding dynamics. We find that ligand binding occurs to pre-folded G4 structures and that Phen-DC3 also induces G4 formation in unfolded single strands. Following ligand binding to dynamically populated G4s, the DNA undergoes pronounced conformational redistributions that do not involve direct ligand-induced G4 conformational interconversion. On the contrary, the redistribution is driven by ligand-induced G4 folding and trapping of dynamically populated short-lived conformation states. Thus, ligand-induced stabilization does not necessarily require the initial presence of stably folded G4s.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EF15_003%2F0000477" target="_blank" >EF15_003/0000477: Strukturní gymnastika nukleových kyselin: od molekulárních principů přes biologické funkce k terapeutickým cílům.</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chembiochem

ISSN

1439-4227

e-ISSN

1439-7633

Svazek periodika

22

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

8

Strana od-do

1811-1817

Kód UT WoS článku

000625227700001

EID výsledku v databázi Scopus

2-s2.0-85101924712